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Melasma is a chronic pigmentary disorder that presents significant therapeutic challenges due to its recurrent nature and variable response to conventional treatments. It predominantly affects photo exposed facial areas and often impacts patient’s quality of life. Microneedling is an established technique for melasma management, promoting skin renewal and enhancing the transdermal delivery of depigmenting agents. Recently, exosomes have emerged as a novel therapeutic approach with regenerative and pigment-modulating potential. This pilot randomized controlled clinical trial aimed to assess the efficacy and safety of microneedling combined with topical exosomes compared to microneedling alone in the treatment of melasma. Twelve female participants were randomized into two groups: one treated with microneedling and topical application of exosomes, the other with microneedling and saline solution as control group. Outcomes were evaluated through clinical assessment using MASI and GAIS scales. The combination group showed greater reduction in melasma severity and improved aesthetic appearance than the control group. No adverse effects were reported. These findings suggest that exosomes may enhance the therapeutic efficacy of microneedling. This approach represents a promising and safe alternative for melasma management and supports further investigation into exosome-based dermatological therapies.